Chronic kidney disease (CKD) is a major risk factor for death, cardiovascular disease, and hospitalization. Cardiovascular disease is also associated with CKD. Together these conditions are among the leading causes of death and disability in the U.S. Small studies have found that left ventricular hypertrophy and subclinical cardiovascular disease are predictors of progression of CKD in non-diabetic patients and the elderly. These findings suggest that cardiovascular disease may lead to kidney injury and kidney function decline. This relationship has not been sufficiently explored. Specific Aim #1 of this project will determine the cross-sectional association of subclinical alterations in cardiac structure and function and biomarkers of early kidney injury in an ethnically diverse cohort of men and women (Multi-Ethnic Study of Atherosclerosis). Specific Aim #2 will determine the longitudinal association between subclinical alterations in cardiac structure and function, kidney function decline, and incident chronic kidney disease within the same cohort. All data analysis will be performed by the applicant Dr. Park. The pattern of kidney injury and disease that results from cardiac disease is also unknown. Use of novel urinary biomarkers such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may allow differentiation between different etiologies of rise in creatinine experienced by patients with heart failure, as these are elevated in cases of clinically diagnosed acute tubular necrosis but not in cases of clinically diagnosed pre-renal azotemia.21,26 Specific Aim #3 will characterize the associations of acute decompensated heart failure with biomarkers of kidney injury, kidney recovery, and length of hospital stay in a de novo cohort recruited at the University of California, San Francisco Medical Center. Understanding the effect of early and late heart disease on the kidneys will be crucial to our understanding of risk factors for kidney disease progression to end-stage renal disease. The pathways of CKD progression are not well understood. While many factors are at work, subclinical and clinical cardiovascular disease undoubtedly plays an important role. Detection and characterization of kidney disease by biomarkers of kidney injury may become an important tool for future management strategies in this setting and others. PUBLIC HEALTH RELEVANCE: We believe that heart disease is a major cause of kidney disease and the process begins in the early stages of both conditions, before the disease is even able to be detected by conventional methods. This project will investigate the interaction of the heart and kidney using new methods. These methods may help to diagnose and treat millions of individuals in the U.S. living with heart and kidney disease.